Skip to main content
OpenTrials
Completed

NCT Number: NCT04625036

NO-mediated Vascular Function in Covid-19 Patient

The 2019 coronavirus-induced infection (COVID-19) has caused a pandemic that has spread worldwide. Up to date, many subjects affected by the virus report important sequelae on different organs increasing morbidity and exacerbating previous pathological conditions. Mortality is also increased in cases of comorbidities such as cardiovascular disease, hypertension and diabetes. COVID-19 infection is caused by Coronavirus-2 (SARS-CoV-2). Concerning the specific interaction of SARS-CoV-2 with the cardiovascular system, we know that this virus enters the body through the receptors for the conversion of angiotensin II (ACE2r) that are present in the lungs, heart, intestinal epithelium and vascular endothelium. This receptor's availability suggests a multi-organ involvement with a consequent multi-organ dysfunction, as found in patients affected by SARS-CoV-2 infection.

Furthermore, poor vascular peripheral function -usually correlated with old age and long periods of bed rest or hypomobility- is a distinguishing characteristic of the population affected by COVID-19, as well. Thus, it is reasonable to expect that peripheral vascular function, already deteriorated by aging and common age-related diseases, can be further compromised by COVID-19 and by the forced hypomobility, typically experienced during the acute phase of the disease.

The main aim of this project will be to investigate the peripheral NO-mediated vascular function in the leg of patients recovering from Covid-19 pneumonia.

A significant vascular dysfunction is expected to be found in post COVID individuals and to be correlated to the relevant clinical variables.

Completed

Looking for future studies?

Notify Me

Key information

Age range

30 year–80 year

Sex eligibility

All sexes

Study type

Observational

Primary location

ICS Maugeri IRCCS, U.O. Emergenza Coronavirus di Lumezzane

Lumezzane, Brescia, 25065, Italy

About this study

The 2019 coronavirus-induced infection (COVID-19) has caused a pandemic that has spread worldwide, causing approximately 250,000 deaths to date. Even if the contagion curves seem to stabilize, many subjects have been affected by the virus and report important sequelae on the cardiovascular system. This can be explained by the assumption that COVID-19 interacts with the cardiovascular system at different levels, increasing morbidity and exacerbating previous pathological conditions. Mortality is, in fact, increased in cases of comorbidities such as cardiovascular disease, hypertension and diabetes.

COVID-19 infection is caused by Coronavirus-2 (SARS-CoV-2). This virus enters the body through the receptor for the conversion of angiotensin [angiotensin-converting enzyme 2, ACE2]. This receptor is present in the lungs, heart, intestinal epithelium and vascular endothelium. The receptor's availability suggests a multi-organ dysfunction, as found in patients affected by SARS-CoV-2 infection. In particular, the infection of endothelial cells or pericytes, as well as the cytokine-mediated inflammatory cascade induced by the infection, can lead to severe microvascular and macrovascular dysfunctions.

It is important to underline that endothelial damage is one of the precursors of the atherosclerosis and endothelial dysfunction is related to pulmonary, cardiac and neurological diseases. Furthermore, poor vascular function is related to old age and long periods of bed rest or hypomobility, those characteristics are present in the population affected by COVID-19, as well. Thus, it is reasonable to expect that peripheral vascular function, already deteriorated by aging and common age-related diseases, can be further compromised by COVID-19 and by the forced hypomobility typically experienced during the acute phase of the disease.

Recently, the endothelial function mediated by nitric oxide (NO) has been easily and non-invasively investigated on common femoral artery with the ultrasound technique of Single Passive Leg Movement. The main aim of this project will be to investigate the NO-mediated vascular function in patients recovering from Covid-19 pneumonia, within one month from discharge in order to verify the presence of endothelial dysfunction acutely induced by the viral infection.

The secondary aim will be to evaluate the correlation between NO-mediated vascular function (evaluated by ultrasound technique) and age, anthropometric parameters (height, weight, Body Mass Index), clinical parameters, oxygenation status, physical performance and pharmacology.

The data will be analysed with the Shapiro-Wilk test to evaluate their "normality" and will be presented as mean ± standard deviation (sd) or median (interquartile range) depending on the type of distribution detected. Correlation tests (Pearson/Spearman) between ultrasound evaluation on peripheral blood flow and vessels and oxygenation levels, clinical, anthropometric and physical performance measures will then be performed. Values of p <0.05 will be considered significant.

A significant peripheral vascular dysfunction is expected to be found in post COVID individuals and to be correlated to relevant clinical variables (i.e. muscle strength, respiratory parameters, oxygenation status).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of COVID-19 pneumonia
  • Clinical stability condition (temperature <37.5 ° C, Respiratory Rate (RR) <22 breaths/min, Heart Rate (HR)> 50 beats/minute and <120 beats/minute, absence of major arrhythmias, hemodynamic stability)
  • Possibility to reach the sitting position independently

Exclusion criteria

-Previous cardiovascular, respiratory, neurological or orthopaedic diseases.

Treatment and study plan

Single passive leg movement

Diagnostic Test

The investigation consists of a non-invasive evaluation by ultrasounds performed on the common femoral artery investigating the speed of arterial blood flow [Leg Blood Flow LBF] and diameter of vessel with a dedicated ultrasound system (General Electric Medical Systems, Milwaukee, WI) using Doppler method, before and after a passive flexion-extension movement of the knee. A linear probe will be used with a frequency of 5 MHz. Using the diameter of the artery and the average volume (Vmean), the LBF will be calculated every second with the formula=Average volume*PiGreco*(vessel diameter / 2)2*60.

The subject will be placed in a sitting position for 20 minutes before the test. The protocol consists of image acquisition for 60 seconds (basal measurement), followed by a passive flexion-extension of the knee (single passive leg movement). The knee flexion will be performed by health care personnel at a rate of 1 Hz. At the end of the movement, the recording will continue for 60 seconds.

Primary outcomes

  1. Leg Blood Flow

    Time frame: Baseline

    Leg Blood Flow will be analyzed with an ultrasound examination using the Single Passive Leg Movement technique.

    In particular, the investigation consists of an ultrasound performed on the common femoral artery using Doppler method with a linear probe with a frequency of 5 MHz.

    The subject will be placed in a sitting position at rest for 20 minutes before the test is performed. The protocol consists of image acquisition for 60 seconds (basal measurement), followed by a passive flexion-extension of the knee performed by health care personnel at a rate of 1 Hz. At the end of the movement, the recording will continue for another 60 seconds.

Secondary outcomes

  1. Clinical evaluations

    Time frame: Baseline

    Routinary measures as single anthropometric data: height (cm) and weight (Kg) and aggregate measure as body mass index (Kg/m2)

  2. Clinical characteristics

    Time frame: Baseline

    Clinical course of disease (days) will be noted for all subjects

  3. Presence of device

    Time frame: Baseline

    Ventilatory support (yes or no) will be noted for all subjects

  4. Therapy

    Time frame: Baseline

    Drug therapy (list of drugs) will be noted for all subjects

  5. Clinical characteristics

    Time frame: Baseline

    Number of comorbidities will be noted for all subjects

  6. Biochemical evaluations - ProBNP

    Time frame: Baseline

    All subjects will perform blood tests to investigate bio-humoral data. Normal values: <125 pg/mL

  7. Biochemical evaluations - D-dimer

    Time frame: Baseline

    All subjects will perform blood tests to investigate bio-humoral data. Normal values:<500 ng/mL FEU

  8. Biochemical evaluations - PCR

    Time frame: Baseline

    All subjects will perform blood tests to investigate bio-humoral data. Normal values:<=5.00 mg/L

  9. Functional evaluations - 1-Minute Sit To Stand

    Time frame: Baseline

    Therapists ask the participants to sit down on a chair without armrests. The assisted use of the arms is not allowed during the STS test. The therapists instruct the participants to complete as many sit-to-stand cycles as possible within 60 s at self-paced speed and count the number of fully-completed STS cycles. Normal values: 50/min-27/min.

  10. Functional evaluations - 6-Minute Walking Test

    Time frame: Baseline

    The 6MWT is a self-paced test of walking capacity. Patients will be asked to walk as far as possible in 6 min along a flat corridor. The distance in metres is recorded. Standardised instructions and encouragement are given during the test.

    Predicted 6MW Distance follows this calculation: 361-(age in yrs x 4) + (height in cm x 2) + (HRmax/HRmax % pred x 3) - (weight in kg x 1.5) - 30 (if females).

  11. Functional evaluations - Biceps' muscle strength with dynamometer

    Time frame: Baseline

    The patient will be seated with the elbow flexed 90" and forearm supinated; the dynamometer will be positioned just proximal to styloid processes and the patient will be asked to flex his elbow. Prediction equation=229.421-84.836*(0=male, 1=female) +0,165*weight-1.503*age.

  12. Functional evaluations - Quadriceps' muscle strength with dynamometer

    Time frame: Baseline

    The patients will be seated with hips and knees flexed 90''; the dynamometer will be positioned just proximal to malleoli and the patient will be asked to extend his knee. Prediction equation=358.455-87.581*(0=male, 1=female) +0.297*weight-3.136*age

Sponsors and collaborators

Lead sponsor

Istituti Clinici Scientifici Maugeri SpA

Other

Collaborators

  • Universita di Verona

Registry information

Official study title

Pilot Study on Peripheral Vascular Function in Covid-19 Patient

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Nov 12, 2020
Registry last updated
Apr 14, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.